ABSTRACT Heart diseases are the No.1 cause of death in the US and developed world, but effective drug therapies are still lacking. In order to develop better and more effective therapies to treat heart diseases, it is critically important for physicians and scientists to gain accurate and in-depth understanding of the cellular and molecular mechanisms of heart diseases. In recent decades, researchers in the field have been accumulating more and more experimental data from molecular, to cellular, and to tissue and organ levels. However, important conceptual advances in the cardiac field require integration of the knowledge from multiple scales. Here we take the necessary step forward to integrate experimental data into quantitative models that enable using mathematical tools and computational power to understand the complex interactions of the cells and molecules in the heart. The unique design of this conference series is to combine experimental study and mathematical modeling to achieve in-depth understanding of the non- linear dynamic systems that control cardiac function and heart diseases. This conference is the 6th in our interdisciplinary symposium series entitled ?System?s Approach to Understand Cardiac Excitation-Contraction Coupling?. The previous 5 conferences have received overwhelmingly positive evaluations from scientific community and resulted in numerous high impact publications. This proposed conference will continue the uniquely interdisciplinary format to combine experimental and modeling studies in the field of cardiac arrhythmias. The topics will be focused on the cutting-edge research in cardiac excitation, Ca2+ signaling, contraction mechanics and mechanotransduction, with emphases on integrating the the dynamic systems to gain a holistic and comprehensive understanding of heart diseases. The goal of this conference will be focused on (1) summarizing current state of research in the focus area, (2) identifying consensus and controversy that warrant more investigation, (3) exchanging ideas, data, and information among the experimentalists and modelers to facilitate interdisciplinary collaborations. The conference results will be summarized in the form of white papers to be published in leading scientific journals that have broad impact in heart disease field.